Niemelä Anssi M, Hynninen Piritta, Mecklin Jukka-Pekka, Kuopio Teijo, Kokko Antti, Aaltonen Lauri, Parkkila Anna-Kaisa, Pastorekova Silvia, Pastorek Jaromir, Waheed Abdul, Sly William S, Orntoft Torben F, Kruhøffer Mogens, Haapasalo Hannu, Parkkila Seppo, Kivelä Antti J
Department of Surgery, Jyväskylä Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, Finland.
Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1760-6. doi: 10.1158/1055-9965.EPI-07-0080.
Carbonic anhydrase (CA) II, CA IX, and CA XII are expressed in various neoplasias and have been linked to tumorigenesis. We examined their expression in three different groups of colorectal cancer [i.e., microsatellite stable (MSS), microsatellite instable (MSI), and hereditary nonpolyposis colorectal cancer (HNPCC)]. First, we analyzed gene expression profiles of 113 specimens by a microarray method to study the expression of various CA isozymes in the subgroups of colorectal cancer. The results indicated that mRNAs for CA II and CA XII are down-regulated and CA IX mRNA is up-regulated in all three tumor categories when compared with the normal tissue. The up-regulation of CA IX was greatest in the HNPCC group. For more information, 77 specimens were immunohistochemically stained to study the levels of CA II, CA IX, and CA XII. Immunohistochemical analyses further confirmed that the subgroups express CA II, CA IX, and CA XII differentially, and the HNPCC tumors express high levels of CA IX. Expression of these CAs did not correlate to Dukes stage or grade of differentiation. Our results show that CAs are differentially expressed in the subgroups of colorectal cancer, and CA IX expression seems to be very high in most cases of HNPCC. CA IX could be a potential diagnostic and therapeutic target in HNPCC.
碳酸酐酶（CA）II、CA IX和CA XII在多种肿瘤中表达，并与肿瘤发生有关。我们检测了它们在三组不同的结直肠癌中的表达情况，即微卫星稳定（MSS）、微卫星不稳定（MSI）和遗传性非息肉病性结直肠癌（HNPCC）。首先，我们通过微阵列方法分析了113个标本的基因表达谱，以研究各种CA同工酶在结直肠癌亚组中的表达。结果表明，与正常组织相比，在所有三种肿瘤类型中，CA II和CA XII的mRNA表达下调，而CA IX的mRNA表达上调。CA IX的上调在HNPCC组中最为明显。为了进一步了解情况，我们对77个标本进行了免疫组织化学染色，以研究CA II、CA IX和CA XII的水平。免疫组织化学分析进一步证实，这些亚组中CA II、CA IX和CA XII的表达存在差异，且HNPCC肿瘤中CA IX表达水平较高。这些CA的表达与Dukes分期或分化程度无关。我们的结果表明，CA在结直肠癌亚组中存在差异表达，且在大多数HNPCC病例中，CA IX的表达似乎非常高。CA IX可能是HNPCC潜在的诊断和治疗靶点。
